IN-VITRO SUSCEPTIBILITIES OF CLINICAL YEAST ISOLATES TO A NEW ECHINOCANDIN DERIVATIVE, LY303366, AND OTHER ANTIFUNGAL AGENTS

LY303366 is a new semisynthetic echinocandin derivative with potent, b road-spectrum fungicidal activity, We investigated the in vitro activi ty of LY303366, amphotericin B, flucytosine (5FC), fluconazole, and it raconazole against 435 clinical yeast isolates (413 Candida and 22 Sac charomyces cerevisiae isolates) obtained from over 30 different medica l centers, MICs for all five antifungal agents were determined by the National Committee for Clinical Laboratory Standards method with RPMI 1640 test medium, LY303366 was also tested in antibiotic medium 3 as s pecified by the manufacturer, Overall, LY303366 was quite active again st all of the yeast isolates when tested in RPMI 1640 (MIG at which 90 % of the isolates are inhibited [MIG(90)], 1.0 mu g/ml) but appeared t o be considerably more potent when tested in antibiotic medium 3 (MIC( 90), 0.03 mu g/ml). When tested in antibiotic medium 3, LY303366 was 1 6- to >2,000-fold more active than itraconazole, fluconazole, amphoter icin B, or 5FC against all species except Candida parapsilosis, When t ested in RPMI 1640, LY303366 was comparable to amphotericin B and itra conazole and more active than fluconazole and 5FC, All of the isolates for which fluconazole and itraconazole had elevated MICs (greater tha n or equal to 128 and greater than or equal to 2.0 mu g/ml, respective ly) were inhibited by less than or equal to 0.007 mu g of LY303366/ml when tested in antibiotic medium 3 and less than or equal to 0.5 mu g/ ml when tested in RPMI 1640, Based on these studies, LY303366 has prom ising antifungal activity and warrants further in vitro and in vivo in vestigation.